As part of our study of proviral integration sties, we have developed a novel application of the polymerase chain reaction (PCR) technique which allows us to amplify small segments of DNA adjacent to a region of known sequence. The basic idea is to cut the cut the DNA with a frequent cutting restriction enzyme such as Sau3A and then to circularize these fragments. Oligonucleotides complementary to opposite strands of DNA from the region of known sequence and pointing 5'leads to 3' away from each other in the original configuration of the linear DNA are then used to amplify the portion of the Sau3A circle which contains the region of unknown sequence. In our case, we are using this method to clone cellular DNA flanking integrated proviruses, but the method promises to be widely applicable to other situations in which one would like to clone DNA adjacent to a previously identified region, such as in "walking" or "jumping" along a chromosome, or in cloning the control region upstream of an mRNA (cDNA) start site.